ArticleProceedings of the National Academy of Sciences of the United States of America2013
Astrocyte pathology and the absence of non-cell autonomy in an induced pluripotent stem cell model of TDP-43 proteinopathy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 219 papers, 1 of them a synthesis that pooled it.
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Who cites it
219 citing papers in PubMed, 1 synthesis or guideline pooled it, 350 citations in OpenAlex.
- What can we learn on ALS pathophysiology from iPSC-derived motor neurons harbouring TARBDP mutations: a systematic review.Translational neurodegeneration · 2026Pooled it
- Modeling human neurodegeneration with iPSCs: opportunities, limitations, and the challenge of aging.The Journal of clinical investigation · 2026Review
- Clusterin is enriched in plaque-associated astrocytes and localizes to synapses in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Reactive astrocytes mediate toxicity in iPSC derived dopaminergic neurons.NPJ Parkinson's disease · 2026Article
- PolyGraph - Flexible, Biocompatible & Electrically Optimized Graphene-Polymer Composites for Next-Generation Neural Interfaces.Advanced healthcare materials · 2026Article
- MYC-driven gliosis impairs neuron-glia communication in amyotrophic lateral sclerosis.Brain : a journal of neurology · 2026Article
- Predictive Cellular Signatures from Live Human Motor Neurons Distinguish TDP-43 ALS and Enable ALS Subtype Stratification.bioRxiv : the preprint server for biology · 2026Article
- Human iPSC-derived motor neurons as a platform for elucidating TDP-43-related amyotrophic lateral sclerosis pathogenesis: a mini review.Frontiers in molecular neuroscience · 2026Review
- Non-cell autonomous autophagy in amyotrophic lateral sclerosis: A new promising target?Neurobiology of disease · 2026Review
- Engineering Cortical Networks: An Open Platform for Controlled Human Circuit Formation and Synaptic Analysis In Vitro.Advanced healthcare materials · 2025Article
- Changes in neural progenitor lineage composition during astrocytic differentiation of human iPSCs.eLife · 2025Article
- Neuroimmune signaling mediates astrocytic nucleocytoplasmic disruptions and stress granule formation associated with TDP-43 pathology.Neurobiology of disease · 2025Article
- Intersecting impact of CAG repeat and huntingtin knockout in stem cell-derived cortical neurons.Neurobiology of disease · 2025Article
- Biomimetic Scaffolds Enhance iPSC Astrocyte Progenitor Angiogenic, Immunomodulatory, and Neurotrophic Capacity in a Stiffness and Matrix-Dependent Manner for Spinal Cord Repair Applications.Advanced healthcare materials · 2025Article
- Endothelial TDP-43 depletion disrupts core blood-brain barrier pathways in neurodegeneration.Nature neuroscience · 2025Article
- Amyotrophic lateral sclerosis and frontotemporal dementia mutation reduces endothelial TDP-43 and causes blood-brain barrier defects.Science advances · 2025Article
- Review
- Review
- TDP43 augments astrocyte inflammatory activity through mtDNA-cGAS-STING axis in NMOSD.Journal of neuroinflammation · 2025Article
- The Rise of Pluripotent Stem Cell-Derived Glia Models of Neuroinflammation.Neurology international · 2025Review
159 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 7 institutions in 2 countries.
Funding
Abstract
Glial proliferation and activation are associated with disease progression in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia. In this study, we describe a unique platform to address the question of cell autonomy in transactive response DNA-binding protein (TDP-43) proteinopathies. We generated functional astroglia from human induced pluripotent stem cells carrying an ALS-causing TDP-43 mutation and show that mutant astrocytes exhibit increased levels of TDP-43, subcellular mislocalization of TDP-43, and decreased cell survival. We then performed coculture experiments to evaluate the effects of M337V astrocytes on the survival of wild-type and M337V TDP-43 motor neurons, showing that mutant TDP-43 astrocytes do not adversely affect survival of cocultured neurons. These observations reveal a significant and previously unrecognized glial cell-autonomous pathological phenotype associated with a pathogenic mutation in TDP-43 and show that TDP-43 proteinopathies do not display an astrocyte non-cell-autonomous component in cell culture, as previously described for SOD1 ALS. This study highlights the utility of induced pluripotent stem cell-based in vitro disease models to investigate mechanisms of disease in ALS and other TDP-43 proteinopathies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.